The association of atherosclerotic cardiovascular disease and statin use with inflammation and treatment outcomes in tuberculosis

Abstract

Tuberculosis (TB) and atherosclerotic cardiovascular disease (ASCVD) have a close epidemiological and pathogenetic overlap. Thus, it becomes essential to understand the relationship between ASCVD and TB outcomes. From our retrospective cohort on drug-susceptible TB patients at the National Taiwan University Hospital, we assessed the association of pre-existing ASCVD (coronary artery disease (CAD) and atherothrombotic stroke (ATS)) with 9-month all-cause and infection-related mortality and the extent of mediation by systemic inflammatory markers. We determined the effect of pre-existing ASCVD on 2-month sputum microbiological status. Among ASCVD patients, we assessed the association of statin use on mortality. Nine-month all-cause mortality was higher in CAD patients with prior acute myocardial infarction (CAD+AMI+) (adjusted HR 2.01, 95%CI 1.38–3.00) and ATS patients (aHR 2.79, 95%CI 1.92–4.07) and similarly, for infection-related mortality was higher in CAD+AMI+ (aHR 1.95, 95%CI 1.17–3.24) and ATS (aHR 2.04, 95%CI 1.19–3.46) after adjusting for confounding factors. Pre-existing CAD (AMI- or AMI+) or ATS did not change sputum culture conversion or sputum smear AFB positivity at 2 months. The CAD+AMI+ group had significantly higher levels of CRP at TB diagnosis in the multivariable linear regression analysis (Adjusted B(SE) 1.24(0.62)). CRP mediated 66% (P = 0.048) and 25% (P = 0.033) of the association all-cause mortality with CAD+AMI− and CAD+AMI+, respectively. In summary, patients with ASCVD have higher hazards of 9-month all-cause and infection-related mortality, with elevated serum inflammation mediating one to three-quarters of this association when adjusted for confounders. Statin use was associated with lower all-cause mortality among patients with ASCVD.

Statins block mammalian target of rapamycin pathway: a possible novel therapeutic strategy for inflammatory, malignant and neurodegenerative diseases

“…Statins also have anti-inflammatory, antioxidant, antiproliferative and immunomodulatory effects (Bahrami et al 2018 ; Parizadeh et al 2011 ; Koushki et al 2021 ). Statins can stabilize atherosclerotic plaques and prevent platelet aggregation as well (Kim et al 2019 ; Chidambaram et al 2021 ). Statins are generally very well tolerated drugs.…”

One-Week Dynamic Changes in Cardiac Proteomes After Cardiac Radioablation in Experimental Rat Model

“…Tuberculosis (TB) is a bacterial infection disease that mostly affects lung but, it could attack other parts of organs such as kidney, brain, and heart. Therefore, cardiac involvement in TB is common and TB infected patients possess a high risk to cause heart failure, constrictive pericarditis, or developing atherosclerotic cardiovascular diseases ( 24 , 25 ). The Cd74 (H-2 class II histocompatibility antigen gamma chain) included in TB pathway is reported that its expression on atherosclerotic plaques, and peripheral blood mononuclear cells (PBMC) with its potential pro-inflammatory responses ( 26 ).…”

Diabetes severity is strongly associated with the risk of active tuberculosis in people with type 2 diabetes: a nationwide cohort study with a 6-year follow-up

“…In one study, TB was associated with an increased risk of acute myocardial infarction (adjusted HR, 1.98; 95% CI, 1.3–3.0) [ 26 ]. Another study found that patients with atherosclerotic CVD had higher HR for all-cause and infection-related mortality after initiation of TB treatment [ 27 ]. Elevated serum markers of inflammation were found to mediate one-quarter to one-third of this association [ 27 ].…”